Foretova Lenka, Machackova Eva, Navratilova Marie, Pavlu Hana, Hruba Marcela, Lukesova Miroslava, Valik Dalibor
Department of Cancer Epidemiology and Genetics, and Laboratory Medicine, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, 656 53 Czech Republic.
Hum Mutat. 2004 Apr;23(4):397-8. doi: 10.1002/humu.9226.
Germline mutations in BRCA1 and BRCA2 account for majority of hereditary breast and ovarian cancer. The complete coding sequence analysis of both genes was carried out in 197 breast/ovarian cancer patients from high-risk families and 53 patients with sporadic breast/ovarian cancer. In summary, 59 mutations (16 different) in BRCA1 and 29 mutations (17 different) in BRCA2 were identified in unrelated breast and/or ovarian index cases. Using the BIC Database numbering, the most frequently found mutations in BRCA1 were c.5385dupC (22 cases), c.3819_3823delGTAAA (8 cases) and c.300T>G (6 cases). The most frequently found mutations in BRCA2 were c.8138_8142delCCTTT (7 cases) and c.8765_8766delAG (7 cases). Altogether, these 5 mutations represented 56.8% of all detected mutations. A broad spectrum of other mutations was detected including four novel mutations (c.2881delA in BRCA1; and c. 6677_6678delAA, c.6982dupT and c.8397_8400dupTGGG in BRCA2). Deleterious mutations were found in 80 (40.6%) of 197 high risk-families, in 6 (37.5%) of 16 patients with sporadic bilateral breast, ovarian or both cancers and in 2 (6.2%) of 32 women with sporadic early-onset unilateral breast cancer. No mutation was detected in 5 cases of sporadic early-onset unilateral ovarian cancer.
BRCA1和BRCA2的种系突变是遗传性乳腺癌和卵巢癌的主要病因。对来自高危家族的197例乳腺癌/卵巢癌患者以及53例散发性乳腺癌/卵巢癌患者进行了这两个基因的完整编码序列分析。总之，在无关的乳腺癌和/或卵巢癌索引病例中，共鉴定出BRCA1基因的59个突变（16种不同突变）和BRCA2基因的29个突变（17种不同突变）。采用BIC数据库编号，BRCA1基因中最常见的突变是c.5385dupC（22例）、c.3819_3823delGTAAA（8例）和c.300T>G（6例）。BRCA2基因中最常见的突变是c.8138_8142delCCTTT（7例）和c.8765_8766delAG（7例）。这5种突变共占所有检测到的突变的56.8%。还检测到了广泛的其他突变，包括4种新突变（BRCA1基因中的c.2881delA；以及BRCA2基因中的c.6677_6678delAA、c.6982dupT和c.8397_8400dupTGGG）。在197个高危家族中的80个（40.6%）、16例散发性双侧乳腺癌、卵巢癌或两者皆有的患者中的6个（37.5%）以及32例散发性早发性单侧乳腺癌患者中的2个（6.2%）发现了有害突变。在5例散发性早发性单侧卵巢癌患者中未检测到突变。
